Plants and animals rely on innate immunity to prevent potential infections by detection of pathogen-associated molecular patterns (PAMPs) through pattern recognition receptors (PRRs). In plants, PAMPs are perceived by cell-surface PRRs and mount PAMP- triggered immunity (PTI). Successful pathogens are able to suppress PTI by producing virulence effectors, which, in turn, are recognized by plant intracellular PRRs to initiate effector-triggered immunity (ETI). This complex host-microbe interaction is intricately intertwined with a wide range of environmental factors. For example, we found that the ambient temperature fluctuation regulates PTI and ETI in a distinct manner. We have developed an Arabidopsis cell system to express individual pathogen effectors for ETI or treat cells with purified PAMPs for PTI. In combination with enriched genetic and genomic resources in Arabidopsis, this synchronized and autonomous plant cell-single pathogen signal system holds significant promise for dissecting the complex regulation of signaling events in ETI and PTI. Our preliminary data strongly suggest the existence of differential early signaling mechanisms underlying two branches of plant innate immunity. In particular, we found that the specific members of a large gene family encoding calcium-dependent protein kinases (CDPKs) play pivotal roles in transducing calcium signature in ETI. Our proposed research will employ a multifaceted approach to further understand the signaling mechanisms underlying plant ETI and PTI. The Specific Aims for this application are the following: 1) Decipher the distinct and convergent gene regulation in ETI and PTI; 2) Elucidate the functions of CDPKs in ETI signaling; 3) Dissect the ambient temperature regulation of innate immunity. Plant PTI and ETI are most similar to Toll-like receptor and NOD-like receptor innate immune signaling pathways in mammals respectively. Thus, our research will contribute to a general understanding of innate immunity and improve our ability to prevent and control infectious diseases. PUBLIC HEALTH RELEVANCE: Understanding the intricately intertwined signal transduction networks acting downstream of various host immune sensors could provide novel avenues to prevent and control infectious diseases. Given that plant cell-surface and intracellular immune sensors are most similar to Toll-like receptor and NOD-like receptor in mammals respectively, our research will have broad impact on the understanding of signaling mechanisms of animal innate immunity.